MicroNeedles No Pain, More Gain?

Today’s finger-piercing lancets draw much less blood than their predecessors did. But they still hurt, say some. Today’s insulin needles are models of precision engineering. But they’re still not comfortable for everyone—especially if they hit a nerve.

Microneedles to the Rescue!

New microneedles that are dwarfed by a human hair do the job with an absolute minimum of discomfort.

Made of plastic, silicon, metal or a mixture of those materials, the needles can be made very small (100 microns wide or even narrower) and very sharp (with an edge less than one micron thick).

Created in small clusters, microneedles can be very short—just long enough to gently punch through the tough outer skin.

Just below the skin, microneedles can work with the interstitial fluid in the layer of skin above the blood vessels and nerves. Research indicates that this fluid can correlate reasonably well with blood glucose, and that this also is a promising location for delivering insulin.

“You could have an extremely compact device that monitors glucose and delivers insulin as needed; you could apply it to the body every day or two and not really feel that it hurts,” says Jeffrey Zahn, PhD, assistant professor of bioengineering at Pennsylvania State University in University Park, Pennsylvania.

Predicts Zahn, “We’ll see microneedles commercialized in the reasonably near future, within three to four years.”

Zahn outlined microneedle research and development at the Diabetes Technology Conference in San Francisco in November 2003.

“A lot of companies are now doing clinical trials on microneedles.”

Material Investigations

Researchers began investigating microneedles for drug delivery in the 1990s.

“Diabetes is the largest disease target”, Zahn says, because “it’s a huge healthcare expenditure and it keeps growing.”

While investigators have built hypodermic microneedles, most of their research is in clusters because the flow of a drug through a single needle is very limited. Getting the right mix of small size and structural rigidity has been a challenge.

Much work has been done in developing silicon microneedles, exploiting the well-mastered processes used to manufacture computer chips.

Silicon is “an extremely stiff material, and it penetrates the skin very well, but it is brittle,” Zahn says. “Metal and polymers can absorb more stress because they can partially deform. But as they try to penetrate the skin, the needles can’t deform enough.”

“Additionally, silicon is an unproven material from the FDA’s point of view, says Dorian Liepmann, associate professor in mechanical engineering at the University of Berkeley, in whose lab Zahn did his first work with microneedles.

As silicon and plastics are studied, early commercial microneedles may be made of conventional stainless steel. That’s the approach taken by SpectRx in Norcross, Georgia, which used an array of five microneedles in a patch for an insulin pump in successful early clinical trials.

At Needle Point

Liepmann and graduate students Boris Stoeber and Stefan Zimmerman have built a prototype glucose meter that attaches with microneedles. The device performs continuous monitoring and is self-calibrating, Liepmann says.

While its measurements of interstitial fluid don’t always match up closely with standard blood glucose meter readings, Liepmann suggests that “when you have a continuous measurement, glucose sensing doesn’t have to be as accurate or precise because you are looking for trends.”

Liepmann and Stoeber also have created a single-use microneedle patch designed to store and deliver freeze-dried vaccines. Liepmann speculates that this design could be reworked to inject glucagon to treat low blood glucose emergencies, although no work has been done on the relevant chemistry and bioengineering requirements.

More in the mainstream, the Berkeley group, as well as researchers at Georgia Tech and elsewhere in academia and industry, have demonstrated prototype microneedle delivery systems. The goal is to develop a complete closed-loop glucose measurement and insulin delivery system in a device the size of a credit card that sits painlessly on your wrist, Zahn says.

“There’s a lot of behind-the-scenes work by diabetes companies,” Zahn says. “Probably a majority are interested in microneedle technology, but they don’t want to invest the resources into commercializing it until the reliability issues are solved. They’re trying to get something that works and has FDA approval before sending out a press release.”

Some firms that have said they are working in this field are Becton Dickinson Diabetes Care in Franklin Lakes, New Jersey; BioValve Technologies of Worcester, Massachusetts; Kumetrix of Union City, California; NanoPass of Haifa, Israel; SpectRx; and Therafuse in San Diego, California.

None will commit to a product date. There are also a host of alternatives for getting under your skin, including jet injectors, electrical currents, heat and ultrasound.

A One-Shot Deal?

“It’s possible that microneedles could replace the syringe,” says David Klonoff, MD, director of the Mills-Peninsula Diabetes Research Institute in San Mateo, California, and editor of the journal Diabetes Technology & Therapeutics.

However, cost is likely to be a big obstacle.

Conventional needles cost about a quarter, and the latest 31-gauge models are only “slightly thicker than a hair,” points out Robert Singley, vice president for marketing and sales at Becton Dickinson Diabetes Care.

You also can buy needles as short as 5 mm, Singley says.

“We keep working on technology that allows us to take the hurt out.”

Other firms innovating with syringes include Inviro Medical Devices of Vancouver, which offers a model that safely retracts the needle after use.

Singley also predicts a massive shift in the United States toward pen delivery systems, which may feature the smallest needles.

Will HMOs Feel Your Pain?

Regardless of how they are used, microneedles will be more expensive to design, test and manufacture than conventional needles. The cost issues get trickier because of research studies indicating that if you don’t focus on the insulin needle as it goes in, it just doesn’t hurt that much, says Klonoff, who has participated in tests that show that adults often can’t tell they’ve had an injection or else say that it didn’t really hurt.

“Most of us get our first injections with much larger needles, so we expect a shot to hurt,” says Singley. With the latest 31-gauge needles, “it feels like a pinch—although if you hit a nerve, it’s going to hurt.”

“A 32-gauge conventional needle is 300 microns wide, which is quite small,” says Zahn. “We have to show that more expensive microneedle techniques work better, and prove it to HMOs.”

SpectRX Granted Second Patent for Patch Infusion Set

On December 16, 2003, SpectRx, Inc. of Norcross, Georgia, announced it was granted a second significant patent for its SimpleChoice patch insulin pump infusion set.

The patch is for use with insulin pumps worn by people with diabetes to control their insulin levels.

According to SpectRx, the FDA-cleared patch is designed for use with most insulin pumps on the market today.

“The patch delivers insulin through five microneedles that are much shorter and thinner than ordinary insulin pump infusion needles,” says SpectRx. “The reduced depth of penetration is designed to improve comfort and the overall pump experience.”

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